The pregnancy outcome prediction (POP) study: Investigating the relationship between serial prenatal ultrasonography, biomarkers, placental phenotype and adverse pregnancy outcomes

Placental dysfunction is implicated in many major complications of pregnancy associated with adverse maternal and infant outcome, such as preeclampsia, fetal growth restriction and stillbirth. Yet, despite years of intensive research, screening for these complications is still largely based upon clinical grounds rather than ultrasonic and/or biochemical assessment of placental function. One of the few widely employed methods for assessment of risk, low first trimester levels of PAPP-A (Pregnancy Associated Plasma Protein A), was identified through secondary analysis of data collected to identify new methods of screening for Down's syndrome rather than as a purposeful search for screening tests for abnormal placentation. Development of improved methods for population screening requires better mechanistic understanding of the pathways leading to placentally-related complications of human pregnancy. This is in addition to a need for identification of biomarkers which reflect the underlying pathology, while predicting associated disease with high sensitivity and specificity. In this paper, we outline some of the challenges and opportunities in this area. Furthermore, we illustrate how some of these can be addressed in research studies using the example of the Pregnancy Outcome Prediction (POP) study, a prospective cohort study conducted in Cambridge, UK.This study was funded by the NIHR Cambridge Comprehensive Biomedical Research Centre [grant number A019057], the Medical Research Council [grant number MR/K021133/1] and the Stillbirth and Neonatal Death Society (SANDS)

Advice for Health Care Professionals and Users: An Evaluation of Websites for Perinatal Anxiety

Background: Many websites are available with information and resources for perinatal anxiety; however, there is limited research on the quality and content of these sites. Objective: This study aims to identify what sites are available on perinatal anxiety, identify any information and therapeutic advice given, and review its accuracy and website design. Methods: We conducted an evaluation of websites for perinatal anxiety. Eligible websites (N=50) were evaluated for accuracy of information, resources for mothers, website quality, and readability. Results: Information was often incomplete and focused on symptoms rather than risk factors or impact of untreated perinatal anxiety. Websites often had information on treatment (46/50, 92%), but much less on screening (19/50, 38%). Most sites provided at least some resources to support mothers (49/50, 98%), but active, guided support was infrequent (25/50, 50%). Website quality was extremely variable and mostly difficult to read (42/50, 84%). Conclusions: This study recommends the top 4 websites on perinatal anxiety for health care professionals and users. There is a need for websites to be developed that provide accurate, evidence-based information that women can relate to with quality support resources. Furthermore, these sites should be easy to use and readable

Determination of zeolite-group mineral compositions by electron probe microanalysis

A new protocol for the quantitative determination of zeolite-group mineral compositions by electron probe microanalysis (wavelength-dispersive spectrometry) under ambient conditions, is presented. The method overcomes the most serious challenges for this mineral group, including new confidence in the fundamentally important Si-Al ratio. Development tests were undertaken on a set of natural zeolite candidate reference samples, representing the compositional extremes of Na, K, Cs, Mg, Ca, Sr and Ba zeolites, to demonstrate and assess the extent of beam interaction effects on each oxide component for each mineral. These tests highlight the variability and impact of component mobility due to beam interaction, and show that it can be minimized with recommended operating conditions of 15 kV, 2 nA, a defocused, 20 μm spot size, and element prioritizing with the spectrometer configuration. The protocol represents a pragmatic solution that works, but provides scope for additional optimization where required. Vital to the determination of high-quality results is the attention to careful preparations and the employment of strict criteria for data reduction and quality control, including the monitoring and removal of non-zeolitic contaminants from the data (mainly Fe and clay phases). Essential quality criteria include the zeolite-specific parameters of R value (Si/(Si + Al + Fe3+), the ‘E%’ charge-balance calculation, and the weight percent of non-hydrous total oxides. When these criteria are applied in conjunction with the recommended analytical operating conditions, excellent inter-batch reproducibility is demonstrated. Application of the method to zeolites with complex solid-solution compositions is effective, enabling more precise geochemical discrimination for occurrence-composition studies. Phase validation for the reference set was conducted satisfactorily with the use of X-ray diffraction and laser-ablation inductively-coupled plasma mass spectroscopy

Current trends in fluid and blood product availability in small animal practices in the UK

Objectives To investigate and discuss current fluid and blood products stocked in small animal practices in the UK. Methods An online survey was circulated to small animal veterinary practices across the UK. The survey included questions regarding the level of hospital care provided, the type of fluid and blood component products stocked, the most frequently restocked products, and the available options in the event that blood products were required but not stocked. Results There were 423 responses including 27 duplicates. The remaining 396 respondents represented a spectrum of practices including 19 referral practices. Crystalloids were stocked in all practices. Lactated Ringer's solution was the most frequently re‐stocked product in 355 of 396 (90%) of practices. Where synthetic colloids were stocked, gelatin‐based colloids (155/178 [87%]) were stocked in preference to hydroxyethyl starches (23/178 [13%]). Blood products were stocked by 81 of 396 (20%) of practices. If a blood product was required but not stocked, 31% of practices would use a pet blood banking service, 28% would use their own blood donors, and 21% would refer. Clinical Significance This study provides an insight into the fluid and blood products stocked and used by a selection of veterinary practices within the UK and serves as a baseline for ongoing research and decision‐making in both veterinary practice and industry

The Maillard reaction in traditional method sparkling wine.

The Maillard reaction between sugars and amino acids, peptides, or proteins generates a myriad of aroma compounds through complex and multi-step reaction pathways. While the Maillard has been primarily studied in the context of thermally processed foods, Maillard-associated products including thiazoles, furans, and pyrazines have been identified in aged sparkling wines, with associated bready, roasted, and caramel aromas. Sparkling wines produced in the bottle-fermented traditional method (Méthode Champenoise) have been the primary focus of studies related to Maillard-associated compounds in sparkling wine, and these wines undergo two sequential fermentations, with the second taking place in the final wine bottle. Due to the low temperature (15 ± 3°C) and low pH (pH 3-4) conditions during production and aging, we conclude that Maillard interactions may not proceed past intermediate stages. Physicochemical factors that affect the Maillard reaction are considered in the context of sparkling wine, particularly related to pH-dependent reaction pathways and existing literature pertaining to low temperature and/or low pH Maillard activity. A focus on the origins and composition of precursor species (amino acids and sugars) in sparkling wines is presented, as well as the potential role of metal ions in accelerating the Maillard reaction. Understanding the contributions of individual physicochemical factors to the Maillard reaction in sparkling wine enables a clearer understanding of reaction pathways and sensory outcomes. Advancements in analytical techniques for monitoring the Maillard reaction are also described, and important areas of future research on this topic are identified.The Brock Library Open Access Publishing Fun

A structural and biochemical model of processive chitin synthesis

Chitin synthases (CHS) produce chitin, an essential component of the fungal cell wall. The molecular mechanism of processive chitin synthesis is not understood, limiting the discovery of new inhibitors of this enzyme class. We identified the bacterial glycosyltransferase NodC as an appropriate model system to study the general structure and reaction mechanism of CHS. A high throughput screening-compatible novel assay demonstrates that a known inhibitor of fungal CHS also inhibit NodC. A structural model of NodC, on the basis of the recently published BcsA cellulose synthase structure, enabled probing of the catalytic mechanism by mutagenesis, demonstrating the essential roles of the DD and QXXRW catalytic motifs. The NodC membrane topology was mapped, validating the structural model. Together, these approaches give insight into the CHS structure and mechanism and provide a platform for the discovery of inhibitors for this antifungal target

The human homologue of unc-93 maps to chromosome 6q27 – characterisation and analysis in sporadic epithelial ovarian cancer

BACKGROUND: In sporadic ovarian cancer, we have previously reported allele loss at D6S193 (62%) on chromosome 6q27, which suggested the presence of a putative tumour suppressor gene. Based on our data and that from another group, the minimal region of allele loss was between D6S264 and D6S149 (7.4 cM). To identify the putative tumour suppressor gene, we established a physical map initially with YACs and subsequently with PACs/BACs from D6S264 to D6S149. To accelerate the identification of genes, we sequenced the entire contig of approximately 1.1 Mb. Seven genes were identified within the region of allele loss between D6S264 and D6S149. RESULTS: The human homologue of unc-93 (UNC93A) in C. elegans was identified to be within the interval of allele loss centromeric to D6S149. This gene is 24.5 kb and comprises of 8 exons. There are two transcripts with the shorter one due to splicing out of exon 4. It is expressed in testis, small intestine, spleen, prostate, and ovary. In a panel of 8 ovarian cancer cell lines, UNC93A expression was detected by RT-PCR which identified the two transcripts in 2/8 cell lines. The entire coding sequence was examined for mutations in a panel of ovarian tumours and ovarian cancer cell lines. Mutations were identified in exons 1, 3, 4, 5, 6 and 8. Only 3 mutations were identified specifically in the tumour. These included a c.452G>A (W151X) mutation in exon 3, c.676C>T (R226X) in exon 5 and c.1225G>A(V409I) mutation in exon 8. However, the mutations in exon 3 and 5 were also present in 6% and 2% of the normal population respectively. The UNC93A cDNA was shown to express at the cell membrane and encodes for a protein of 60 kDa. CONCLUSIONS: These results suggest that no evidence for UNC93A as a tumour suppressor gene in sporadic ovarian cancer has been identified and further research is required to evaluate its normal function and role in the pathogenesis of ovarian cancer